The goal of this project is to produce the full length outer-membrane proteins from different stages of the malaria parasite in a secreting yeast expression system. The purpose for the production of these recombinant proteins is to provide sufficient quantities of the outer-membrane proteins from both the sporozoite stage and the sexual stage of Plasmodium falciparum to test as vaccine candidates. Previous results have indicated that irradiated sporozoites injected into human subjects provide protection against malaria challenge. Attempts at using the tetrapeptide repeats of the circumsporozoite protein (CSP), the major antigen on the infective sporozoite, resulted in limited success in generating antibody to the sequences, and failure in providing predictable protection to humans. It has been postulated that other primary sequences in the CSP may be necessary as T-helper sites, hepatocyte receptor-binding sites or other B- cell epitopes. To study the function, immunogenicity and potential suitability of the full length peptide for vaccine use, we have ligated the CSP gene from P. falciparum into a specially constructed vector which promotes maturation of the CSP through the plasma membrane of Saccharomyces cerevisiae. We have found three forms of the recombinant DNA-derived CSP which have been secreted from the yeast cell (-80% yield). ELISA and RIPA results indicate that these forms are antigenically similar to the authentic CSP. The major species of this protein are 50-55 kDa, 60-65 kDa and 85-90 kDa. These species will be purified and their immunogenic potential tested in conjunction with a viral construct of the same protein. A second antigen, the 25 kDa protein, represents a major antigen of the zygote and ookinete form of the sexual stage. A gene representing the truncated form of the 25kDa protein is being cloned into a secreting yeast system and into an adenoviral vector. This recombinant protein may be important in stimulating transmission blocking antibodies in humans.